OBINUSS - A trial to evaluate a new drug in systemic sclerosis: obinutuzumab.

Trial details

Who runs it

Assistance Publique Hopitaux De Paris

Trial code

EU 2025-524003-68-00

Record updated

2026. július 28.

Original description

The main objective of this study is to show a decrease of both skin and lung fibrosis, as evaluated by the revised Composite Response Index in SSc, 360 days from randomisation, in patients with diffuse SSc treated with obinutuzumab when compared to patients treated with a placebo.Read full original descriptionShow less

OBINUSS - Safety and efficacy of obinutuzumab in systemic sclerosis: a phase II, randomized, double-blinded versus placebo-controlled trial

The main objective of this study is to show a decrease of both skin and lung fibrosis, as evaluated by the revised Composite Response Index in SSc, 360 days from randomisation, in patients with diffuse SSc treated with obinutuzumab when compared to patients treated with a placebo.

Inclusion: 1-Adult patient (>/= 18 years old),; 10- Anti-fibrotic drugs such as nintedanib is permitted; 2-Patient with a diagnosis of SSc, as defined by the American College of Rheumatology / EULAR 2013 criteria,; 3-Patient with a diffuse SSc, as defined according to Leroy et al; 4-Patient with a SSc disease duration of less than 8 years (defined as time from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined by EUSTAR disease activity score,; 5- Patient with a modified Rodnan skin score (mRSS) > /= 10 and < /= 35 units at screening,; 6-Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception during the treatment period and up to 18 months after stopping it; 7-Patient able to give written informed consent prior to participation in the study,; 8-Affiliation to a social security scheme (profit or being entitled); 9- If patients receive mycophenolate or methotrexate for SSc, these need to be on stable dose as follows: Mycophenolate mofetil/sodium: stable dose for at least 2 months prior to randomisation Methotrexate: stable dose and route of administration for at least 2 months prior to randomisation.

Exclusion: 10-Active infection of any kind, excluding fungal infection of the nail beds. Any major episode of infection that also fulfills any of the following criteria: * Requires hospitalization during the 8 weeks prior to screening or during screening * Requires treatment with IV antibiotics (or anti-infectives) during the 8 weeks prior to screening or during screening * Requires treatment with oral antibiotics (or anti-infectives) during the 2 weeks prior to screening or during screening * Antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary; 14-Major surgery requiring hospitalization during the 4 weeks prior to or during screening; 15-Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening; 2-Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening; 21- Patients treated with CAR-T cell immunotherapy; 3-Any biologic therapy (other than anti-CD20, anti-CD19, or anti-plasma cell) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening; 4-Inhibitors of Janus-associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening; 5-Any live vaccine during the 28 days prior to screening or during screening; 6-High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions during the 28 days prior the screening; 11-History of serious recurrent or chronic infection; 12-History of progressive multifocal leukoencephalopathy (PML); 13-History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years (Participants with non-melanomatous carcinomas of the skin that have been treated or excised and have resolved are eligible); 16-Intolerance or contraindication to study therapies, including any of the following: *History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion; 7-Active infection with SARS-CoV-2 or patients not fully vaccinated following national recommendations against SARS-CoV-2; 8-Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation; 9-HIV infection: for participants with unknown HIV status, HIV testing will be performed locally at screening if required by local regulations; 1-Any B-cell depleting (e.g., anti-CD20, anti-CD19) or anti-plasma cell therapy such as, but not limited to, obinutuzumab, rituximab, ocrelizumab, ofatumumab, or bortezomib less than 9 months prior to screening or during screening. If anti-CD20 or anti-CD19 therapy has been received between 9 and 12 months prior to screening, the peripheral CD19+ B-cell count must be over 25 cells/µL; 17-Any of the following laboratory parameters: *AST or ALT above 2.5 upper limit normal range * Neutrophils <1.5x103/mL * Positive hepatitis B surface antigen (HBsAg) Participants who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring until 12 months after the last dose of obinutuzumab or placebo. * Positive hepatitis C serology Participants with positive hepatitis C antibody test result with no detectable hepatitis C virus (HCV) RNA for at least 6 months after completion of antiviral therapy are eligible but will require monthly HCV RNA monitoring until 12 months after the last dose of obinutuzumab or placebo. * Hemoglobin below 7 g/dL * Platelet count below 50,000/L; 18-Pregnant or breastfeeding woman, or woman who refuses to use an effective contraception during the study course; 19-Protected adults (including individual under legal guardianship by court order or curatorship) or adults deprived of liberty; 20-Patient participating in another investigational therapeutic study in the 3 months preceding inclusion.

EU CTIS 2025-524003-68-00